6-Fluoro-3,5-dichloro-2-pyridinyl phosphorus compounds

ABSTRACT

Compounds are prepared which correspond to the formula ##STR1## wherein R represents alkyl of 1 to 4 carbon atoms and R 1  represents OR, amino or mono- or dialkylamino wherein each alkyl group is of 1 to 4 carbon atoms. These compounds have been found to be highly active in the kill and control of soil insects.

SUMMARY OF THE INVENTION

The compounds of the present invention are6-fluoro-3,5-dichloro-2-pyridinyl phosphorothioates which correspond tothe formula ##STR2## wherein R represents alkyl of 1 to 4 carbon atomsand R¹ represents OR, amino or mono- or dialkylamino wherein each alkylgroup is of 1 to 4 carbon atoms.

The compounds of the present invention are oily liquids or solids atambient temperatures and are soluble in many common organic solvents,such as, for example, carbon tetrachloride, acetone, toluene, methylenechloride, dimethylformamide and the like, and are of low solubility inwater. These compounds have exceptional activity in the kill andcontrol, when employed in insecticidally effective amount, of soilinsects especially the larvae of the Western spotted cucumber beetle.These active compounds may be formulated with the usual insecticidecarriers, well known to those skilled in the art, to provideinsecticidal compositions for the above use. The compounds of thepresent invention can be prepared by a variety of methods. In one suchmethod, an alkali metal salt of 6-fluoro-3,5-dichloro-2-pyridinol,formed insitu, is reacted with an appropriate phosphorochloridothioatein the presence of an inert organic solvent. This reaction can becharacterized as follows: ##STR3## wherein X, R and R¹ are ashereinbefore set forth and M represents sodium, potassium, lithium orcesium. No attempt has been made to present a balanced equation. Ifdesired, the reaction can be carried out in the presence of a catalyst.

In carrying out the above process, the alkali metal salt is usuallyprepared first by providing a mixture of the pyridinol startingmaterial, alkali metal carbonate, and the solvent. This mixture isheated at from about 25° C. to about 50° C., with agitation, untilformation of the alkali metal salt of the pyridinol takes place, usuallyfrom about 1 to about 2 hours. At this time, the appropriate phosphorousreactant is added thereto. The resulting reaction mixture is maintainedat about 15° C. to about 100° C., with agitation, until the reaction issubstantially complete usually from about 1 to about 8 hours.

Upon completion of the reaction, the product mixture is cooled, theinsolubles filtered therefrom and the solvent is removed. The residue istaken up with a solvent such as methylene chloride and washed withwater. The methylene chloride layer is dried, filtered and distilledunder reduced pressure to remove the solvent therefrom. The resultingproduct can be used as prepared, however, if desired, it can be furtherpurified by conventional techniques known to those skilled in the art.

Ordinarily, substantial equimolar proportions of the pyridinol andphosphorus reactants and the alkali metal carbonate are employed.However, the alkali metal carbonate and the pyridinol starting materialcan be employed in slight excess of the stoichiometric requirements inorder to insure the obtainment of the highest yields.

Catalysts useful in carrying out the present process include tertiaryamines having a pKa of at least about 9.5 as taught in U.S. Pat. No.3,928,370; co-catalyst which are mixtures of quaternary ammonium asphosphonium salts and organic tertiary amines such as taught in U.S.Pat. No. 3,907,815; 3,917,621; 4,007,197 and 4,016,225 which includesquaternary ammonium compounds such as tetraalkyl ammonium salts, such astetra-n-butyl-, tetrahexyl-, tri-n-butyl methyl-, cetyl trimethyl-,trioctyl methyl- and tridecyl methyl ammonium chlorides, bromides,bisulfates, tosylates, etc.; arylalkylammonium salts, such astetrabenzyl- ammonium chloride, benzyl trimethyl-, benzyl trimethyl-,benzyl triethyl-, benzyl tributyl-, and phenethyl-trimethylammoniumchlorides, bromides, etc.; arylammonium salts, such as triphenylmethylammonium fluoride, chloride or bromide, N,N,N-trimethylaniliniumbromide, N,N-diethyl-N-methylanilinium bisulfate, trimethyl naphthylammonium chloride, p-methylphenyl trimethyl ammonium chloride ortosylate, etc.; 5- and 6-membered hetrocyclic compounds containing atleast one quaternized nitrogen atom in the ring, such asN-methylpyridinium chloride or methyl sulfate, N-hexyl pyridiniumiodide, (4-pyridyl)-trimethylammonium chloride,1-methyl-1-azabicyclo[2.2.1]heptane bromide, N-N-dibutylmorpholiniumchloride, N-ethylthiazolium chloride, N-butylpyrrolium chlorides, andthe like; additionally, mercuric chloride and other such materials knownfor use in similar preparative procedures can also be employed.

The following examples illustrate the present invention and the mannerby which it can be practiced, but, as such, should not be construed aslimitations upon the overall scope of the same.

EXAMPLE I O,O-Dimethyl O-(3,5-dichloro-6-fluoro-2-pyridinyl)phosphorothioate ##STR4##

A mixture was prepared by admixing, with stirring, 20 grams (g) (0.11mole (m)) of 3,5-dichloro-6-fluoro-2-pyridinol, 16 g (0.116 m) ofpotassium carbonate, 0.2 g of mercuric chloride and 250 milliliters (ml)of acetonitrile. To this mixture, with stirring, was added dropwise 16 g(0.1 m) of O,O-dimethyl phosphorochloridothioate. After the addition wascomplete, the mixture was stirred for an additional 0.5 hour and thenheated to about 50° C., with stirring, for 2 hours. The reaction mixturewas cooled to room temperature and filtered to remove insolubles. Thesolvent was removed by evaporation under reduced pressure. The residuewas dissolved in 100 ml of benzene and washed with water. The organiclayer was dried and filtered. The benzene was removed by evaporation.The residue (20 g of an oil) was crystallized from 30 ml of hexane togive 13 grams of O,O-dimethyl O-(3,5-dichloro-6-fluoro-2-pyridinyl)phosphorothioate. The product, a solid, melted at room temperature andhad a refractive index of n_(d) ²⁵ =1.5370. Upon analysis, the productwas found to have carbon, hydrogen and nitrogen contents of 27.40, 2.28and 4.27 percent, respectively, as compared with the theoreticalcontents of 27.46, 2.31 and 4.58 percent, respectively, as calculatedfor the above compound.

EXAMPLE II O,O-Diethyl O-(3,5-dichloro-6-fluoro-2-pyridinyl)phosphorothioate ##STR5##

A mixture was prepared by admixing, with stirring, 9.7 g (0.053 m) of3,5-dichloro-6-fluoro-2-pyridinol, 5.6 g (0.053 m) of sodium carbonateand 100 ml of dimethylformamide. To this mixture was added all at once,at room temperature, with stirring, 9.9 g (0.053 m) of O,O-diethylphosphorochloridothioate. The resulting mixture was heated at 60°-65° C.with stirring for one hour. The mixture was cooled to room temperatureand filtered to remove insolubles. The solvent was removed bydistillation under reduced pressure and the residue dissolved in 100 mlof benzene. The mixture was washed with water and the organic layerseparated, dried and filtered. The benzene was removed by evaporationunder reduced pressure. The residue (15 g) was crystallized from 15 mlof hexane giving 5.9 g of the desired O,O-diethylO-(3,5-dichloro-6-fluoro-2-pyridinyl) phosphorothioate. The productmelted at 31°-33° C. and upon analysis, was found to have carbon,hydrogen and nitrogen contents of 32.30, 3.30 and 4.19 percent,respectively, as compared with the theoretical contents of 32.36, 3.32and 4.19 percent, respectively, as calculated for the above namedcompound.

By following the preparative procedures as set forth hereinaboveincluding Examples I and II and employing the appropriate startingreactants, the following compounds are prepared.

O,O-dipropyl O-(3,5-dichloro-6-fluoro-2-pyridinyl) phosphorothioate,having a molecular weight of 362.19;

O,O-Di-Butyl O-(3,5-dichloro-6-fluoro-2-pyridinyl) phosphorothioate,having a molecular weight of 390.24;

O-Methyl O-(3,5-dichloro-6-fluoro-2-pyridinyl)isopropylphosphoramidothioate, melting at 71°-73° C.;

O-Methyl O-(3,5-dichloro-6-fluoro-2-pyridinyl)methylphosphoramidothioate, having a molecular weight of 269.09;

O-Butyl O-(3,5-dichloro-6-fluoro-2-pyridinyl)di-butylphosphoramidothioate, having a molecular weight of 410.37;

The compounds of the present invention have been found to be useful forthe kill and control of the undesirable agricultural insects of theclass known as soil insects, and especially in the kill and control ofinsects such as the larvae of the Western Spotted Cucumber Beetle. Thecompounds are highly active and both kills the insects outright andprevents adult emergence from the juvenile forms of the insects. In suchapplications, the insect to be controlled and/or its habitat iscontacted or treated with an insecticidally-effective amount of one ormore of the compounds of the present invention.

For all such uses, these compounds can be employed in unmodified form.However, the present invention embraces the use of aninsecticidally-effective amount of the active ingredients in compositionform with a chemically inert material known in the art as an adjuvant orcarrier.

Thus, for example, compositions employing one or a combination of theseactive ingredients can be in the form of a liquid, a granule, a dust,wettable powder or the like; and the adjuvant employed can be any one ofa plurality of materials including aromatic solvents, petroleumdistillates, propellant substances, surface-active dispersing agents,light absorbers and finely-divided carrier solids.

The exact concentration of one or a combination of the compounds of thepresent invention in a composition thereof with an adjuvant therefor canvary; it is only necessary that one or a combination of the compounds bepresent in a sufficient amount so as to make possible the application ofan insecticidally-effective or inactivating dosage.

Suitable adjuvants of the foregoing type are well known to those skilledin the art. The methods of applying the solid or liquid insecticidalformulations are similarly well known in the art.

The insecticidally-effective dosage desirable for effective use ofpreparations containing active compounds will naturally depend onvarious factors such as the active ingredient or ingredients chosen andthe form of preparation. Moreover, the activities of the compounds ofthe present invention against different insects will vary from compoundto compound. Generally, for practical applications, one or a combinationof these active ingredients can be broadly applied to the insect larvaeor their habitat in compositions containing from about 0.001 percent toabout 98 percent by weight of the compounds.

In the preparation of dust compositions, these compounds can becompounded with any of the finely-divided carrier solids such aspyrophyllite, diatomaceous earth, gypsum and the like. In suchoperations, the finely-divided carrier is ground or mixed with one or acombination of the compounds, as active agent(s), or wetted with asolution of the active agent(s) in a volatile organic solvent.Similarly, dust compositions can be compounded with various soliddispersing agents, such as fuller's earth, attaplugite and other clays.These dust compositions can be employed as treating compositions or canbe employed as concentrates and subsequently diluted with additionalsolid dispersing agents or with pyrophyllite, diatomaceous earth, gypsumand the like to obtain the desired amount of active agent in a treatingcomposition. Also, such dust compositions can be dispersed in water,with or without the aid of a surfactant, to form spray mixtures.

Furthermore, one or a combination of the compounds or a dust concentratecomposition containing such compound(s) can be incorporated in intimateadmixture with surface-active dispersing agents such as ionic andnonionic emulsifying agents to form spray concentrates. Suchconcentrates are readily dispersible in liquid carriers to form sprayscontaining the toxicant(s) in any desired amount. The choice of thedispersing agent and amount thereof employed are determined by theability of the agent to facilitate the dispersion of the concentrate inthe liquid carrier to produce the desired spray composition.

Granular formulations are usually prepared by impregnating a solution ofthe toxicant in a volatile organic solvent onto a bed of coarselydivided attapulgite, bentonite, diatomite, organic carriers such asground corn cobs, walnut hulls, or the like.

In the preparation of liquid compositions, one or a combination of theproducts can be compounded with a suitable water-immiscible organicliquid and surface-active dispersing agent to produce an emulsifiableliquid concentrate which can be further diluted with water and oil toform spray mixtures in the form of oil-in-water emulsions. In suchcompositions, the carrier comprises an aqueous emulsion, that is, amixture of water-immixcible solvent, emulsifying agent and water.Preferred dispersing agents to be employed in these compositions are oilsoluble and include the nonionic emulsifiers such as the polyoxyethylenederivatives of sorbitan esters, complex ether alcohols and the like.However, soil-soluble-ionic emulsifying agents such as mahogany soapscan also be used. Suitable organic liquids to be employed in thecompositions include petroleum oils and distillates, toluene, liquidhalohydrocarbons and synthetic organic oils.

An aeorsol preparation according to the invention is obtained in theusual manner by incorporating the active substance and a solvent in avolatile liquid suitable for use as a propellant, such as the mixture ofchlorine and fluorine derivatives of methane and ethane commerciallyavailable under the trademark FREON®.

When utilizing the active ingredients of the present invention, one or acombination of the active ingredients or a composition containing suchis applied to the insects or to their habitat in any convenient manner,for example, by means of hand dusters or sprayers or by simple mixingwith the food to be ingested by the insects or larvae. Application tothe foliage of plants is conveniently carried out with power dusters,broom sprayers and fog sprayers. In such foliar applications, thecompositions to be employed should not contain any appreciable amountsof any phytotoxic diluents. In large scale operations, dusts or lowvolume sprays can be applied from aircraft.

EXAMPLE III

Seventy-five grams of air-dried soil were placed in an 8-ouncecontainer. To the soil was added sufficient volume of a 400 ppm aqueousdispersion, prepared by admixing a predetermined amount of one of thehereinafter set forth compounds, dissolved in a suitable inert solvent,with a predetermined amount of water and a predetermined amount of asurfactant, to give various predetermined concentrations of the toxicantin the soil on a soil-chemical basis. The treated soil was air-dried andthoroughly mixed. To each treated container, and control containerstreated with water and surfactant alone, was added 0.5 milliliters of anaqueous suspension of the eggs of the Western Spotted Cucumber Beetle(WSCB) (70-80 eggs of 3-4 days old). Additional treated soil was used tocover the eggs and a sprouted corn seed was placed in the soil andcovered with additional treated soil. The containers were thereaftermaintained under conditions conducive to the growth of the seeds and thehatching of the eggs. Ten to twelve (10-12) days after treatment, thecontainers and the plants therein were examined to determine the minimumconcentration in parts of active compound per million parts of theultimate dispersion necessary to give at least a 100 percent kill andcontrol of the larvae from the hatched eggs. The results of thisexamination are set forth below in Table 1.

                  TABLE 1                                                         ______________________________________                                                             Minimum                                                                       Concentration in PPM                                                          of active compound                                                            in soil to give a LC.sub.100                             Active Compound      of WSCB larvae                                           ______________________________________                                        O,O-Dimethyl O-(3,5-dichloro-                                                 6-fluoro-2-pyridinyl) phosphoro-                                              thioate              1.5                                                      O,O-Diethyl O-(3,5-dichloro-6-                                                fluoro-2-pyridinyl) phosphoro-                                                thioate              1.5                                                      O-Methyl O-(3,5-dichloro-6-fluoro-                                            2-pyridinyl) isopropylphosphor-                                               amidothioate         50.0*                                                    ______________________________________                                         *Insect testedSouthern Corn Rootworm                                     

Preparation of Starting Materials

The 3,5-dichloro-6-fluoro-2-pyridinol employed as starting material is aknown compound and can be prepared as taught in U.S. Pat. No. 3,923,822wherein 3,5-dichloro-2,6-difluoropyridine is reacted with aqueous sodiumhydroxide under autogeneous pressure at a temperature of from 100° to200° C. followed by acidification of the product.

The phosphorus starting materials are known compounds and methods ofpreparing the same are well known to those skilled in the art.

What is claimed is:
 1. A compound corresponding to the formula ##STR6##wherein R represents alkyl of 1 to 4 carbon atoms and R¹ represents OR,amino or mono- or dialkylamino wherein each alkyl group is of 1 to 4carbon atoms.
 2. A compound as defined in claim 1 wherein R¹ is OR. 3.The compound of claim 2 which is O,O-dimethylO-(3,5-dichloro-6-fluoro-2-pyridinyl) phosphorothioate.
 4. The compoundof claim 2 which is O,O-diethyl O-(3,5-dichloro-6-fluoro-2-pyridinyl)phosphorothioate.
 5. The compound as defined in claim 1 which isO-methyl O-(3,5-dichloro-6-fluoro-2-pyridinyl)isopropylphosphoramidothioate.
 6. A composition useful for the kill andcontrol of soil insects which comprises an insecticidally-effectiveamount of a compound corresponding to the formula ##STR7## wherein Rrepresents alkyl of 1 to 4 carbon atoms and R¹ represents OR, amino ormono- or dialkylamino wherein each alkyl group is of 1 to 4 carbonatoms, in admixture with a chemically inert adjuvant therefor.
 7. Acomposition as defined in claim 6 wherein R¹ is OR.
 8. The compositionof claim 7 wherein the compound is O,O-dimethylO-(3,5-dichloro-6-fluoro-2-pyridinyl) phosphorothioate.
 9. Thecomposition of claim 7 wherein the compound is O,O-diethylO-(3,5-dichloro-6-fluoro-2-pyridinyl) phosphorothioate.
 10. Thecomposition as defined in claim 6 wherein the compound is O-methylO-(3,5-dichloro-6-fluoro-2-pyridinyl) isopropylphosphoramidothioate.